School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory, Tianjin Neurosurgery Institute, Tianjin Huan Hu Hospital, Tianjin, 300100, China.
J Mol Neurosci. 2018 Apr;64(4):491-500. doi: 10.1007/s12031-018-1049-7. Epub 2018 Mar 3.
The aim of our study is to build a framework for a better understanding of high-grade glioma (HGG) prognostic-related biomarkers. Whole-genome gene expression microarray was performed to identify differently expressed genes between HGGs and low-grade diffuse gliomas. Several machine learning algorithms were used to filter prognostic-related genes. One hundred ninety-three HGG patients after surgical resection were selected for survival analysis. Immunohistochemistry were performed on these tumor samples to analyze IDH1 mutation status and protein expression of WEE1. qRT-PCR, western blotting, transwell assays, and scratch wound healing assays were performed to evaluate the effect of WEE1 knockdown or overexpression in HGG cells. Three prognostic-related genes (WEE1, IGF2PB3, and EMP3) were demonstrated to separate HGG patients into two different survival subgroups. The area under receiver operating characteristic curve of WEE1 was higher than that of IGF2BP3, EMP3, age, IDH status, 1p/19q status, and MGMT promoter status. WEE1 was an independent covariate compared with IDH status, age, and WHO grade. Knockdown or overexpression of WEE1 can inhibit or promote migration and invasion in U251 and U87 cell lines. WEE1, EMP3, and IGF2BP3 are reliable prognostic-related genes at the mRNA level. WEE1 is an independent prognostic biomarker in survival analysis and has potential diagnostic value for HGG patients. WEE1 can induce HGG cell migration and invasion in vitro.
我们的研究旨在建立一个更好地理解高级别神经胶质瘤（HGG）预后相关生物标志物的框架。通过全基因组基因表达微阵列来识别 HGG 与低级别弥漫性神经胶质瘤之间差异表达的基因。使用几种机器学习算法来筛选预后相关基因。选择 193 名接受手术切除后的 HGG 患者进行生存分析。对这些肿瘤样本进行免疫组织化学分析，以分析 IDH1 突变状态和 WEE1 蛋白表达。进行 qRT-PCR、western blot、transwell 分析和划痕愈合试验，以评估 WEE1 在 HGG 细胞中敲低或过表达的效果。三个预后相关基因（WEE1、IGF2PB3 和 EMP3）被证明可以将 HGG 患者分为两个不同的生存亚组。WEE1 的接受者操作特征曲线下面积高于 IGF2BP3、EMP3、年龄、IDH 状态、1p/19q 状态和 MGMT 启动子状态。与 IDH 状态、年龄和 WHO 分级相比，WEE1 是一个独立的协变量。敲低或过表达 WEE1 可以抑制或促进 U251 和 U87 细胞系的迁移和侵袭。WEE1、EMP3 和 IGF2BP3 是可靠的预后相关基因。WEE1 是生存分析中的独立预后生物标志物，对 HGG 患者具有潜在的诊断价值。WEE1 可以在体外诱导 HGG 细胞迁移和侵袭。
